Twelve male subjects took part in a study to investigate the effects of overfeeding a high-fat diet (19.17 MJ/d; 58% energy from fat) for 2 weeks on plasma cholecystokinin (CCK) levels, food intake, and subjective feelings of hunger and fullness. Before and after the diet, subjects completed a 2-week weighed dietary inventory, formal measurements of food intake from a pre-selected appetizing evening meal were carried out, and blood samples were taken after a standard breakfast for measurement of CCK. Hunger and fullness were rated on visual analogue scales before and after each of these meals and at evening meals during the diet period. Following the high-fat diet there was a small non-significant increase in food intake from the pre-selected meal (6919 (SE 615) kJ v. 6405 (SE 540) kJ; P = 0.1) and a significant increase in the average daily food consumption measured from the diaries (10.25 (SE 0.49) MJ/d v. 9.59 (SE 0.62) MJ/d; P = 0.05). Corresponding trends of increasing feelings of hunger and declining fullness also occurred over the study period. Plasma CCK responses to the standard breakfast were raised following the diet (1285 (SE 153) v. 897 (SE 78) pM min; 3 h integrated CCK production post v. pre diet; P < 0.01) with the major differences observed at 90 and 120 min following the meal. These results suggest that the increase in food intake may be related to a down-regulation in putative CCK receptors responsible for food intake. Elevated CCK levels might suggest a corresponding down-regulation in CCK receptors responsible for feedback inhibition of CCK release.